The antibody responses to meningococcal O-acetylated (OAc+) Group C Polysaccharide (GCPS) and GCPS lacking O acetyl groups (OAc-) were compared in sera from adults vaccinated with GCPS vaccine, from carriers of Group C N. meningitidis and from non carriers. All the sera bound equally well to OAc+ and OAc- GCPS coated plates in an ELISA. The specificity of the antibody response to the two kinds of GCPS was examined by inhibition experiments with various concentrations of either GCPS. Greater inhibition of carrier sera was observed with homologous PS than with heterologous PS. There was substantial inhibition of vaccinee sera with homologous OAc+ PS while OAc- PS inhibited the binding to a significantly smaller extent. Almost no homologous inhibition was observed with OAc- PS when monoclonal Antibodies (McAb) which had more affinity to OAc-than OAc+ GCPS were used. The reason for this remains unclear. There are common epitopes on both OAc+ and OAc- PS due to the presence of the same backbone and unique epitopes due to presence and absence of O-acetyl groups. The proportion of unique antibody specificities present against the two PS is probably different in the sera of vaccinees and carriers. Studies are under way to examine whether McAb and human sera are recognizing different epitopes on the two PS.